期刊
HYPERTENSION
卷 53, 期 4, 页码 682-U172出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.108.118919
关键词
high-density lipoprotein; angiotensin AT1 receptor; endothelial function; diabetes mellitus
资金
- European Foundation
- GRK 865 (Vaskulare Regulations-mechanismen)
- Nachwuchsforderungsstipendium of the Charite
- Excellentiefinanciering KU Leuven [EF/05/013]
- Instituut voor de Aanmoediging van Innovatie en Technologie in Vlaanderen
There is growing evidence that a cross-talk exists between the renin-angiotensin (Ang) system and lipoproteins. We investigated the role of high-density lipoprotein (HDL) on Ang II type 1 receptor (AT1R) regulation and subsequent Ang II-mediated signaling under diabetic conditions. To investigate the effect of HDL on AT1R expression in vivo, apolipoprotein A-I gene transfer was performed 5 days after streptozotocin injection. Six weeks after apolipoprotein A-I gene transfer, the 1.9-fold (P=0.001) increase of HDL cholesterol was associated with a 4.7-fold (P < 0.05) reduction in diabetes mellitus-induced aortic AT1R expression. Concomitantly, NAD(P)H oxidase activity, Nox 4, and p22(phox) mRNA expression were reduced 2.6-fold, 2.0-fold, and 1.5-fold (P < 0.05), respectively, whereas endothelial NO synthase dimerization was increased 3.3-fold (P < 0.005). Apolipoprotein A-I transfer improved NO bioavailability as indicated by ameliorated acetylcholine-dependent vasodilation in the streptozotocin-Ad. hapoA-I group compared with streptozotocin-induced diabetes mellitus. In vitro, HDL reduced the hyperglycemia-induced upregulation of the AT1R in human aortic endothelial cells. This was associated with a 1.3-fold and 2.2-fold decreases in reactive oxygen species and NAD(P) H oxidase activity, respectively (P < 0.05). Finally, HDL reduced the responsiveness to Ang II, as indicated by decreased oxidative stress in the hyperglycemia+HDL+Ang II group compared with the hyperglycemia+Ang II group. In conclusion, vascular-protective effects of HDL include the downregulation of the AT1R. (Hypertension. 2009;53:682-687.)
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